Structure elucidation of colibactin and its DNA cross-links
Structure elucidation of colibactin and its DNA cross-links
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DOI：
10.1126/science.aax2685
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发表时间：
2019-09-06
期刊：
影响因子：
56.9
通讯作者：
Crawford, Jason M.
中科院分区：
文献类型：
--
作者：
Xue, Mengzhao;Kim, Chung Sub;Crawford, Jason M.
大肠杆菌素是由一些具有遗传毒性的肠道大肠杆菌菌株产生的复杂次级代谢产物。大肠杆菌素产生菌的存在与人类结直肠癌的频率和严重程度相关。然而，由于大肠杆菌素尚未被分离或结构表征，研究大肠杆菌素产生菌在人类肠道中的生理作用一直很困难。我们结合遗传学、同位素标记、串联质谱和化学合成来推断大肠杆菌素的结构。我们的结构分配占所有已知的生物合成和细胞生物学数据，并建议在大肠杆菌素基因簇中的最终未知酶的作用。
Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.